The research objectives are to examine the biochemical and morphological events taking place at the synapse which are involved in nerve conduction: (a) to determine the constituency and function of the post-synaptic density, and (b) to determine the mechanism whereby the chemical transmitters are released from the pre-synaptic cell, to affect the post-synaptic cell. With regard to (a), the specific objectives are to extend the tentative identification, by gel electrophoresis, amino acid composition and enzymatic and other biochemical methods, of the major proteins in the density, from that of the already known actin, neurofilament protein, Ca ions-dependent modulator protein (CDR), two receptor proteins for a cAMP-dependent protein kinase, a Mn ions-dependent cyclic AMP phosphodiesterase, a cAMP-Mg ions-protein kinase and CDR-dependent protein kinase; to examine the ways by which these proteins are constructed into the structure, using affinity chromatography and various dissolution methods; and to examine the possible function of the density with regard to synaptic conduction by depolarizing synaptosomes and looking for changes in the protein composition and for changes in the present known biochemical parameters of the subsequently isolated density. With regard to (b), the mechanism of action of the black widow spider toxin, alpha-latrotoxin, in effecting release of neurotransmitters and depletion of synaptic vesicles in brain cortex will be investigated. Specifically the nature of the receptor protein for the specific binding of the toxin will be determined by gel electrophoresis and immunology, using radioactive toxin. The effect of the toxin on Ca ions uptake, on cAMP-dependent and -independent phosphorylation of synaptosomal proteins, on adenylate cyclase, cyclic phosphodiesterase and protein carboxymethylase will be examined, and the effect of the toxin on a possible relocation of Ca ions binding and phosphorylated proteins between synaptic vesicles, synaptic membrane, and even post-synatic densities will be looked for.